Xue, W., Krasnitz, A., Lucito, R., Sordella, R., Van Aelst, L., Cordon-Cardo, C., Singer, S., Kuehnel, F., Wigler, M. H., Powers, S., Zender, L., Lowe, S. W. (June 2008) DLC1 is a chromosome 8p tumor suppressor whose loss promotes hepatocellular carcinoma. Genes & Development, 22 (11). pp. 1439-44. ISSN 0890-9369
![[thumbnail of Paper]](https://repository.cshl.edu/style/images/fileicons/application_pdf.png) |
PDF (Paper)
DLC1 is a chromosome 8p tumor suppressor whose loss promotes.pdf - Published Version Restricted to Repository staff only Download (559kB) |
Abstract
Deletions on chromosome 8p are common in human tumors, suggesting that one or more tumor suppressor genes reside in this region. Deleted in Liver Cancer 1 (DLC1) encodes a Rho-GTPase activating protein and is a candidate 8p tumor suppressor. We show that DLC1 knockdown cooperates with Myc to promote hepatocellular carcinoma in mice, and that reintroduction of wild-type DLC1 into hepatoma cells with low DLC1 levels suppresses tumor growth in situ. Cells with reduced DLC1 protein contain increased GTP-bound RhoA, and enforced expression a constitutively activated RhoA allele mimics DLC1 loss in promoting hepatocellular carcinogenesis. Conversely, down-regulation of RhoA selectively inhibits tumor growth of hepatoma cells with disabled DLC1. Our data validate DLC1 as a potent tumor suppressor gene and suggest that its loss creates a dependence on the RhoA pathway that may be targeted therapeutically.
Actions (login required)
 |
Administrator's edit/view item |